This research grant is developed as a joint effort of the Division of Urology (Department of Surgery) and the Human Immunobiology Group in the Department of Microbiology and Immunology to 1) obtain comprehensive knowledge about the effect of bladder cancer on important host defense mechanisms (the immune system and inflammatory processes) and on the specific immune response to this cancer; 2) explore new therapeutic approaches to bladder cancer by direct immune manipulations (immunotherapy); 3) search for viral agents that may contribute to the etiology of this tumor. Cell-mediate immunity to bladder cancer has been quantified by in vitro methods. Expression of cell-mediated immunity (CMI) appears to require the presence of critical amounts of tumor material in vivo. The nature of the lymphoid cells mediating CMI is being further explored, using surface markers such as Fc receptors. This approach should help to obtain purer populations of effector cells to further increase the sensitivity of in vitro assays for CMI, and to elucidate their mode of action. The effect of tumor stage on specific B and T lymphoid cell and macrophage function are being evaluated with specific reference to prognostic significance. Bladder cancer patients show significantly lower blood lymphocyte stimulation index (response to four different doses of PHA) when compared to normals. All patients have undergone skin testing with the recall antigens: mumps, measles, monilia and Streptokinase/Streptodonase. The host inflammatory response was evaluated with Croton Oil and the ability to be sensitized to a new antigen was tested with dinitrochlorobenzene (DNCB). Patients with localized disease tend to be more responsive in these tests. Immunotherapy with the non-specific immune adjuvant, Corynebacterium parvum is being evaluated by randomized trials in patients with bladder cancer. The initial phase of this work involves exploration of the dose schedule that can be best tolerated. Intravenous and subcutaneous routes are being explored through a ten fold range of C. parvum. The effect of this agent on immune functions is being followed by serial blood tests. Virologic studies of human bladder cancer are directed to the possible role of oncornaviruses in the etiology of human bladder cancer. Using methods of molecular hybridization, subcellular fraction of tumor will be compared with the kno (Text Truncated - Exceeds Capacity)